Nicotine Induces Cardiomyocyte Hypertrophy Through TRPC3-Mediated Ca/NFAT Signalling Pathway.

Background: Nicotine is thought to be an important risk factor for the development of cardiovascular diseases. However, the effects of nicotine on cardiomyocyte hypertrophy are poorly understood. The present study was designed to explore the role of nicotine in cardiomyocyte hypertrophy and its underlying mechanism.

Methods: We used primary cardiomyocytes isolated from Wistar rats to examine the effects of nicotine on intracellular Ca mobilization and hypertrophy determined by immunofluorescence, quantitative polymerase chain reaction, and western blot analysis. A luciferase reporter assay was used to examine the activity of NFAT signalling.

Results: We found that nicotine caused cardiomyocyte hypertrophy, which was accompanied by increased intracellular Ca. Nicotine-enhanced intracellular Ca concentration ([Ca]) was significantly abolished by store-operated Ca entry (SOCE) and TRPC inhibitors. Knockdown of TRPC3 significantly decreased nicotine-induced SOCE and hypertrophy. Moreover, calcineurin-nuclear factor of activated T cells (NFAT) is involved in TRPC3-mediated Ca signalling and cardiomyocyte hypertrophy. Notably, upregulation of TRPC3 by nicotine requires TRPC3-mediated Ca influx and calcineurin-NFAT signalling activation.

Conclusions: Our findings demonstrate that the prohypertrophic effect of nicotine on cardiomyocytes is dependent on enhanced TRPC3 expression through a calcium-dependent regulatory loop, which could become a potential target for prevention and treatment of cardiac hypertrophy.